Differentiation of promyelocytic (HL-60) cells into mature granulocytes: mitochondrial-specific rhodamine 123 fluorescence.

Collins, J M; Foster, Kimberly A.

doi:10.1083/jcb.96.1.94

Cited by 57 publications

(21 citation statements)

References 16 publications

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“…Neutrophils also have a lowered requirement for cytochrome c for the engagement of the intrinsic pathway [28]. We confirmed that neutrophilic differentiation of HL-60 cells is accompanied by decrease in cell stainability with mitochondria-specific dyes [38]. In contrast, we did not observe the previously reported downregulation of cytochrome c [42].…”

Section: Discussioncontrasting

confidence: 33%

“…In HL-60 cells, the differentiation activity of ATRA is mediated through RARα [37], while the mechanism of DMSO action is not clear [36]. However, both inducers cause the G0/G1 cell cycle arrest [13,38] and continuous cell treatment with ATRA or DMSO eventually leads to apoptosis. Both ATRA and DMSO are known to alter the expression of various apoptosis-related genes [12,14,39].…”

Section: Discussionmentioning

confidence: 99%

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Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Vrba¹,

Doležel²,

Ulrichová³

2010

neo

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Histone deacetylases (HDACs) play an important role in regulation of gene expression. Since aberrant upregulation of their activity has been linked to various cancers including leukemic disorders, inhibition of HDACs has emerged as a potential strategy in anticancer therapy. The short chain fatty acids, butyrate and valproate (2-propylvalerate) are effective as HDAC inhibitors at millimolar concentrations [1]. They have been shown to induce, depending on their concentration, monocytic differentiation [2-4] and/or apoptosis in several types of human myeloid leukemic cells [3,[5][6][7]. HDACs have been also identified as molecular targets of all-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL) [8]. Neutrophilic differentiation of normal myeloid cells by ATRA is mediated through the nuclear retinoic acid receptor α (RARα). In the absence of ligand, RARα interacts with nuclear corepressor proteins to form a complex including HDAC1 or HDAC2, resulting in transcriptional repression or silencing. Physiological concentrations of ATRA induce dissociation of the nuclear repressor complex and recruitment of coactivators with histone acetyltransferase activity. This permits the transcriptional activation of differentiation-related genes. In APL cells, the gene encoding RARα appears to be involved in chromosomal translocations, producing several types of RAR-fusion proteins [8,9]. Approximately 98% of APL cases have the t(15;17) translocation leading to the PML-RARα (promyelocytic leukemia protein/RARα) fusion protein. Although ATRA binds to PML-RARα with an affinity comparable to normal RARα, the dissociation of the nuclear repressor complex from PML-RARα and subsequent differentiation occur only at pharmacological doses of ATRA. In contrast, a less common variant of APL with the t(11;17) translocation and the resultant PLZF-RARα (promyelocytic zinc finger protein/RARα) fusion protein has been found resistant to ATRA. This resistance arises from the presence of additional binding site for the nuclear repressor complex in the PLZF moiety of the fusion protein which is insensitive to Received February 3, 2010Differentiation of myeloid leukemic cells may result in less sensitivity to various apoptotic stimuli. We examined whether human leukemia HL-60 cells differentiating by all-trans retinoic acid (ATRA) acquired resistance to the apoptogenic activity of two histone deacetylase (HDAC) inhibitors, butyrate and valproate. In undifferentiated cells, the cytotoxicity of both butyrate and valproate was associated with activation of the intrinsic apoptotic pathway since we observed dissipation of mitochondrial membrane potential, induction of caspase-9 and caspase-3 activities, appearance of sub-G1 DNA and loss of plasma membrane asymmetry and/or integrity. Both HDAC inhibitors were also able to induce accumulation of undifferentiated cells in the G0/G1 phase of the cell cycle. ATRA was found to enhance the apoptotic effect of both butyrate and valproate in undifferentiated cells. This aside, ATRA ...

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Section: Discussioncontrasting

confidence: 33%

Section: Discussionmentioning

confidence: 99%

Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Vrba¹,

Doležel²,

Ulrichová³

2010

neo

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“…Studies of other HL-60 cell populations (Zucker et al, 1983;Collins and Foster, 1983;Ross, 1985), as well as the early volume changes noted in our studies suggested that DMSO and GM CSF might be mediating their opposing growth effects in part through changes in cell cycle kinetics. The results of flow cytometric analysis of HL-60 cells grown in 0-1.5% DMSO and 0% or 10% GCT CM are shown in Table 1.…”

Section: Effects Of Dmso and Gct CM On The Cell Cycle Kinetics Of Hl-mentioning

confidence: 76%

Interactions of dimethyl sulfoxide and granulocyte‐macrophage colony‐stimulating factors on the growth and maturation of HL‐60 cells

Brennan

Lee

Abboud

et al. 1987

Journal Cellular Physiology

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We have studied the interactions of dimethyl sulfoxide (DMSO), Giant Cell Tumor (GCT) cell-conditioned medium (GCT CM), and highly purified granulocyte-macrophage colony-stimulating factors (GM-CSF) on the growth and maturation of a highly passaged population of HL-60 cells. DMSO produced dose-dependent inhibition of HL-60 growth in liquid and semisolid media. Growth was partially to completely restored by the addition of GCT CM to cultures. Experiments in which cell volume, cell cycle kinetics, tritiated thymidine (3HTdr) incorporation, cell number, and nitroblue tetrazolium (NBT) reduction were compared during culture indicated that DMSO inhibited the spontaneous increase in cell volume and flow of cells through the cell cycle which occurred in the first day of culture, the increase in 3HTdr incorporation which was detectable by day 2; and the increment in cell counts which occurred by day 3. These effects were opposed by GCT CM. In contrast, the DMSO-induced increase in NBT reduction which occurred by day 6 was not influenced by GCT CM. The major principle opposing DMSO was GM-CSF, since (1) highly purified GM-CSF from GCT cells and recombinant GM-CSF from COS cells transfected with the Mo cell GM-CSF gene overcame greater than 50% of DMSO inhibition; and (2) conditioned media from cells not producing CSF, G-CSF from GCT cells, and recombinant G-CSF from Escherichia coli transfected with the G-CSF gene from 5,637 cells were inactive. DMSO had little or no effect on the elaboration of autostimulatory activity by HL-60 cells. DMSO is a useful agent for inhibiting the spontaneous growth of HL-60 cells and restoring their dependence on GM-CSF, a property which may be mediated through the effects of DMSO on cell cycle kinetics and/or maturation.

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“…2 Accordingly, inhibitors of glycolysis such as sodium iodoacetate and 2-deoxyglucose caused a profound ATP loss with less than 1% of ATP remaining in comparison to untreated neutrophils ( Figure 1; and data not shown). Moreover, two important mitochondrial enzymes, glutamate dehydrogenase (GDH) and fumarase, which are often used as markers of mitochondria, 10-12 displayed a borderline low activity in neutrophils in contrast to HL-60 cells, which have actively respiring mitochondria 13,14 (Figure 2). At the same time, the activity of the cytoplasmic marker lactate dehydrogenase (LDH) was nearly identical in neutrophils and HL-60 cells, confirming an overall intactness of enzymes in the neutrophil cell lysates (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis

et al. 2003

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Mitochondria are known to combine life-supporting functions with participation in apoptosis by controlling caspase activity. Here, we report that in human blood neutrophils the mitochondria are different, because they preserve mainly death-mediating abilities. Neutrophil mitochondria hardly participate in ATP synthesis, and have a very low activity of the tested marker enzymes. The presence of mitochondria in neutrophils was confirmed by quantification of mitochondrial DNA copy number, by detection of mitochondrial porin, and by JC-1 measurement of Dw m . During neutrophilic differentiation, HL-60 cells demonstrated a profound cytochrome c depletion and mitochondrial shape change reminiscent of neutrophils. However, blood neutrophils containing extremely low amounts of cytochrome c displayed strong caspase-9 activation during apoptosis, which was also observed in apoptotic neutrophil-derived cytoplasts lacking any detectable cytochrome c. We suggest that other proapoptotic factors such as Smac/DIABLO and HtrA2/Omi, which are massively released from the mitochondria, have an important role in neutrophil apoptosis.

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Differentiation of promyelocytic (HL-60) cells into mature granulocytes: mitochondrial-specific rhodamine 123 fluorescence.

Cited by 57 publications

References 16 publications

Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Interactions of dimethyl sulfoxide and granulocyte‐macrophage colony‐stimulating factors on the growth and maturation of HL‐60 cells

Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis

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